How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers’ views

Tafuri, Giovanni; Stolk, Pieter; Trotta, Francesco; Putzeist, Michelle; Leufkens, Hubert G. M.; Laing, Richard; Allegri, Manuela De

doi:10.1093/annonc/mdt512

Cited by 41 publications

(47 citation statements)

References 1 publication

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“…Recent FDA-EMA comparisons show differences in regulatory decisions, route of approval, and availability of cancer drugs that could have important implications for clinical practice and patient safety. [31][32][33][34][35] In particular, regulatory provisions for expediting drug development and approval differ between the US and the EU, 32 with EU regulation being more restrictive in scope. 36 This could lead to divergent outcomes between the two regions.…”

Section: Introductionmentioning

confidence: 99%

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Davis

Naci

Gurpinar

et al. 2017

BMJ

479

415

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Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe. Design Retrospective cohort study. Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013. Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs. Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years’ follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%). Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.

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Section: Introductionmentioning

confidence: 99%

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Davis

Naci

Gurpinar

et al. 2017

BMJ

479

415

View full text Add to dashboard Cite

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“…An interview-based research study indicated that the FDA reviewers tend to have more positive attitude to taking risks than reviewers in the EU (Tafuri et al, 2014). Our study has revealed this tendency objectively in terms of primary endpoints of pivotal clinical trials for marketing authorization.…”

Section: Discussionmentioning

confidence: 56%

Clinical trial designs to obtain marketing authorization of drugs for haematological malignancy in Japan, the EU and the US

Nagai

Ozawa

2016

Br J Haematol

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Differences in regulatory actions between Japan, the European Union (EU) and the United States (US) regarding the approval date and primary endpoints of pivotal trials have never been analysed comprehensively. This study aimed to examine such differences in haematological malignancy indications not only in applications for new molecular entity agents but also in supplemental applications for additional indications. A total of 101 haematological malignancy indications were examined for 58 drugs. Only 30 indications were approved by the regulatory agencies of all three regions with 25, 9 and 67 indications being first approved in Japan, the EU and the US, respectively. Regarding the 18 indications approved only in the US, 13 were approved based on results of single-arm trials. The approval of all nine indications approved first in the EU was based on results of comparative trials. The primary endpoints were different between the EU and the US in 4 of 49 indications approved by both regulatory agencies, all of which were approved earlier in the US than in the EU. This analysis shows that the US Food and Drug Administration has taken the most active attitude to acceptance of surrogate endpoints in single-arm trials. Therefore, not only shorter review time but also this attitude may lead to earlier approval in US.

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“…A likely factor for this lack of coordination is likely attributable to studies that have found DRAs often make different regulatory decisions based upon the same data and may also deal with uncertainty of drug evaluation in fundamentally different ways (i.e. EMA decision for full withdrawal of rosiglitazone from market compared to continued restricted access authorized by the US Food and Drug Administration) [38,39]. Additionally, despite the high occurrence of drug recalls (approximately one per month in the USA), recent work has found that these events are not well publicized by DRAs such as the FDA [40].…”

Section: Discussionmentioning

confidence: 99%

Illicit Internet availability of drugs subject to recall and patient safety consequences

2015

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How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers’ views

Cited by 41 publications

References 1 publication

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13

Clinical trial designs to obtain marketing authorization of drugs for haematological malignancy in Japan, the EU and the US

Illicit Internet availability of drugs subject to recall and patient safety consequences

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